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FLASH GENE
Symbol TRPV1 contributors: shn/npt/pgu - updated : 27-02-2016
HGNC name transient receptor potential cation channel, subfamily V, member 1
HGNC id 12716
Location 17p13.2      Physical location : 3.468.740 - 3.512.705
Synonym name
  • capsaicin receptor
  • vanilloid receptor subtype 1
  • transient receptor potential vanilloid 1a
  • transient receptor potential vanilloid 1b
  • Osm-9-like TRP channel 1
  • Synonym symbol(s) SIC, VR1, DKFZp434K0220, OTRPC1
    DNA
    TYPE functioning gene
    STRUCTURE 43.97 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D17S1798 - D17S1583 - TRPV1 - D17S1298 - D17S1298 - cen
    RNA
    TRANSCRIPTS type messenger
    text Four transcript variants encode the same protein, but with different 5' UTR sequencethree alternative non coding exon 1, splice site flanking exon-intron 7 diverged from the consensus sequence and may help to explain skipping of exon 7 within splice variants
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 4443 95 839 - 1997 9349813
    16 splicing 4074 95 839 - 1997 9349813
    17 splicing 4191 95 839 - 1997 9349813
    16 splicing 4117 95 839 - 1997 9349813
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue   
    Nervousgangliasensory gangliadorsal root   Homo sapiens
     spinal cord     Homo sapiens
    Urinarybladder     Homo sapiens
     kidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Nervousneuron
    Nervousoptic nerve
    Visualganglion cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text spleen
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three N terminal ankyrin (ANK) repeats
  • six transmembrane spanning domains with a pore forming region between transmembrane domains 5 and 6
  • ankyrin repeat
  • six transmembrane domain containing receptor
  • putative coiled-coil domain
  • putative sites for protein kinase A phosphorylation and for N-glycosylation
  • CRAC motifs, cholesterol-binding motifs
  • a C terminal Walker A motif and cytoplasmic tail with a phosphatidylinositol-4,5-bisphosphate binding domain, and a calmodulin binding motif forming an alpha helix that docks into the central cavity of calmodulin (distal C-terminal region was proposed to bind to INPP5J, inhibiting the channels, but it is not required for this binding)
  • mono polymer octamer
    HOMOLOGY
    interspecies homolog to yeast C.elegans F32A6.3
    ortholog to Trpv1, Mus musculus
    ortholog to Trpv1, Rattus norvegicus
    ortholog to TRPV1, Pan troglodytes
    Homologene
    FAMILY
  • temperature-activated transient receptor potential ion channels (thermoTRPs)
  • CATEGORY receptor , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm,nuclear bodies
    text
  • ion channel localized to the plasma membrane and endoplasmic reticulum (ER)
  • basic FUNCTION
  • non selective cation channel, integrating multiple noxious stimuli
  • acts as a molecular detector of noxious stimuli in the peripheral nervous system
  • molecular sensor of noxious heat and capsaicin
  • ion channel that is enriched in sensory neurons and involved in pain perception
  • increasing in intracellular calcium
  • may be involved in the control of emotions, learning, satiety and in integration of painful stimuli
  • mediating inflammatory rather than acute thermal pain
  • acting as proton channel to induce acidification in nociceptive neurons
  • may play a role in non-neuronal mechanisms that might modulate nociception in symptomatic osteoarthritis and rheumatoid arthritis patients
  • has a role in visceral pain and inflammation aggravated by alcohol
  • is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia
  • a role in normal bladder function, particularly in the detection of mechanical stimuli by the urothelium
  • contributes to pressure sensing and ca2+ dependent cell death
  • involved in nuclear translocation of NFkB and the inflammatory cytokine IL-6 with exposure to hydrostatic pressure in vitro
  • may play a role in maintaining normal levels of Ca2+ in retinal ganglion cells
  • plays a key role in the perception of peripheral thermal and inflammatory pain
  • seems to play a significant role in the development of peripheral and central sensitisation and of hyperalgesia and allodynia, and in migraine
  • the outer pore channel of TRPV1 is important for the heat sensitivity of transient receptor potential ion channels
  • essential component of inflammatory hyperalgesia
  • TRPV1 and TRPA1, are necessary for development of inflammatory hypersensitivity and are functionally potentiated by growth factors
  • TRPV1 and TRPA1 induced MUC5B release in the nasal airways
  • TRPV1 agonists induce long-term receptor down-regulation by modulating the expression level of the channel through a mechanism that promotes receptor endocytosis and degradation
  • capsaicin-induced TRPV1 endocytosis and degradation in nociceptors notably contribute to the long-term neuronal tachyphylaxis induced by vanilloids
  • TRPV1 channel has been found to be an important player in the pathway of the detection of chest pain after myocardial injury
  • role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage
  • TRPV1 and TRPA1 in vestibular ganglion (VG) neurons might participate in vestibular function and/or dysfunction such as vertigo
  • TRPA1, like TRPV1, mediates F2RL1-triggered pancreatic nociception and that TRPA1 in collaboration with TRPV1 latently contributes to pancreatitis-related pain
  • plays a critical role in pain associated with tissue injury, inflammation, and nerve lesions
  • central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain
  • TRPV1, TRPA1, and TRPM8 are important to start up a systemic response of energy expenditure, energy allocation, and water retention
  • activation of ASIC3 and TRPV1 as well as enhanced SCN10A activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain
  • regulates the activation and proinflammatory properties of CD4&
  • 8314; T cells
  • cross-talk between ADARA1D and TRPV1, that is involved in the control of prostate carcinoma cell proliferation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    text
  • calcium channel
  • small molecule transport
  • PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphoinositide-interacting regulator of transient receptor potential channels (PIRT)
  • calmodulin
  • Snapin and synaptotagmin IX
  • transient receptor potential cation channel, subfamily V, member 2, TRPV2
  • up-regulation of BDRKB1 may contribute to acute inflammatory pain through TRPV1 activation
  • MYCBP2binteracts with TRPV1 (regulates internalization of TRPV1 in peripheral sensory neurons as well as duration of thermal hyperalgesia through MAPK14)
  • INPP5J is tonically associated with TRPV1 (is now believed to be a TRPV1 agonist, potentiating activation by chemical and thermal stimuli)
  • PIRT and TRPV1 will lie in close proximity and may even form a protein complex
  • is a direct molecular target of the pain-producing molecule phospholipid lysophosphatidic acid (LPA) and this constitutes, the first example of LPA binding directly to an ion channel to acutely regulate its function
  • ARRB2 is a scaffolding protein that regulates TRPV1 receptor activity
  • NOS1 regulates load-induced muscular hypertrophy by activating transient receptor potential cation channel, subfamily V, member 1 (TRPV1)
  • direct anchoring of both PRKACA and ADCY1 to TRPV1 by AKAP5 facilitates the response to inflammatory mediators and may be critical in the pathogenesis of thermal hyperalgesia
  • TRPV1 association with ARRB2 is critical to receptor desensitization via its ability to scaffold the phosphodiesterase PDE4D5 to the receptor, regulating TRPV1 phosphorylation
  • a key region on AKAP79, between AAs 326-336, is responsible for its interaction with TRPV1
  • PIRT increase the sensitivity of TRPV1 channel and modulate its role in heat pain
  • interaction of TRPV1 and TRPA1 signaling pathways (sensitization of TRPV1 via activation of TRPA1, which involves adenylyl cyclase, increased cAMP, subsequent translocation and activation of PKA, and phosphorylation of TRPV1 at PKA phosphorylation residues)
  • disruption of ZBTB20 in nociceptors led to a marked decrease in the expression levels of TRPV1, TRPA1 and TRPM8
  • CALM1 is involved in the Ca(2+)-dependent regulation of TRPV1 via its binding to the TRPV1 C-terminal region
  • TMEM100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner
  • neuronal TRPV1 signaling in periodontal tissue is crucial for the regulation of osteoclastogenesis via the neuropeptide CALCA
  • TRPV1 interacts with ANO1, also called TMEM16A, in primary sensory neurons and this interaction enhanced TRPV1-mediated pain sensation
  • cell & other
    REGULATION
    activated by capsaicin
    increase in temperature in noxious range
    protons
    noxious stimuli
    diverse stimuli, including protons, arachidonic acid metabolites and even painfully hot temperatures (>42 C)
    PIRT
    garlic
    pressure in retinal ganglion cells
    endothelin-1 in the retina
    endocannabinoid anandamide
    noxious heat as well as a wide range of chemical stimuli
    intracellular long-chain acyl CoAs activate TRPV1 channels (
    inhibited by TRPV3
    phosphatidylinositol-4,5-bisphosphate
    vanillotoxins
    Phosphorylated by PRKCE (phosphorylates the ion channel TRPV1 close to a novel microtubule-TRPV1 binding site)
    Other phosphorylated by protein kinase Cepsilon
  • pharmacological desensitization of TRPV1 by PPP3CA may involve additional regulatory components
  • degradation of TRPV1 is mediated by autophagy, and this pathway can be enhanced by cortisol
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    expressed in synovial fibroblasts from osteoarthritis and rheumatoid arthritis patients
    constitutional     --over  
    in injured brachial plexus nerves
    constitutional     --low  
    in nerve fibres in diabetic neuropathy skin that may result from the known decrease of nerve growth factor (NGF) levels
    constitutional     --over  
    in TRPV1 mRNA expression in dorsal root ganglion neurons after injection of complete Freund adjuvant (CFA)-induced inflammation
    constitutional       gain of function
    may contribute to preferential neuronal stress in large dorsal root ganglion neurons relatively early in diabetic sensory neuropathy
    constitutional     --over  
    in hypertrophic hearts, and development of heart hypertrophy is directly associated with increased TRPV1 expression
    Susceptibility rectal hypersensitivity
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    antagonizing the TRPV1-AKAP5 interaction will be a useful strategy for inhibiting inflammatory hyperalgesia
    neurologyacquired 
    more selective therapeutic target than other TRPs for pain and hypersensitivity, particularly in post-traumatic neuropathy
    miscelleaneous  
    antagonising TRPV1 sensitisation is a promising approach and should receive more attention in future research as well as in the development of anti-migraine drugs
    cardiovascular  
    TRPV1 and TRPV2 channels are targets for therapeutic agents of cardiovascular diseases
    neuromuscularmyopathy 
    TRPV1 could be a new therapeutic target for treating muscle atrophy
    ANIMAL & CELL MODELS
  • Vr1-/- mice were viable, fertile, and largely indistinguishable from wildtype littermates but sensory neurons from these mice are severely deficient in their responses to vanilloid compounds, protons, or heat greater than 43 degrees C
  • Trpv1-null mice had more frequent low-amplitude bladder activity than normal mice
  • Trpv1-/- mice had enhanced insulin sensitivity
  • mice lacking Trpv1 pain receptors are long-lived, displaying a youthful metabolic profile at old age